MEDICAMENT FOR DISEASES ASSOCIATED WITH AMYLOID beta AND SCREENING THEREOF

Abstract

The present invention is directed to providing a medicament for treating or preventing a condition, disorder or disease associated with amyloid β. Provided is a method for screening a medicament for treating or preventing a disease associated with amyloid β, the method comprising: A) subjecting at least one of elements selected from the group consisting of 1) exosome; 2) neutral sphingomyelinase 2 (N-SMase2); and 3) sphingomyelin synthetic enzyme 2 (SMS2), and a candidate of the medicament in a condition in which they can interact with each other; and B) examining an influence by the candidate of the medicament to the element, wherein at least one of the elements is used as an index for determining as to whether or not the candidate is the medicament.

1 . A method for screening a treatment substance or prevention substance for a disease associated with amyloid β, comprising:
 (1) allowing protein of neutral sphingomyelinase 2 (N-SMase2) and/or sphingomyelin synthetic enzyme 2 (SMS2) to contact with a test substance; 
 (2) comparing enzyme activity of the protein of the N-SMase2 and/or SMS2 to which the test substance has been contacted, with enzyme activity of protein of the N-SMase2 and/or SMS2 to which the test substance has not been contacted; and 
 (3) when the enzyme activity of the protein of the N-SMase2 to which the test substance has been contacted is increased compared to the enzyme activity of the protein of the N-SMase2 to which the test substance has not been contacted, and/or the enzyme activity of the protein of the SMS2 to which the test substance has been contacted is decreased compared to the enzyme activity of the protein of the SMS2 to which the test substance has not been contacted, selecting the test substance as a treatment substance or prevention substance of the disease associated with amyloid β. 
 
     
     
         2 . A method for screening a treatment substance or prevention substance for a disease associated with amyloid β, comprising:
 (1) allowing a cell to contact with a test substance; 
 (2) comparing expression of N-SMase2 and/or SMS2 in the cell to which the test substance has been contacted, with expression of N-SMase2 and/or SMS2 in a control cell to which the test substance has not been contacted; and 
 (3) when the expression of the N-SMase2 in the cell to which the test substance has been contacted is increased compared to the expression of the N-SMase2 in the control cell to which the test substance has not been contacted, and/or when the expression of SMS2 in the cell to which the test substance has been contacted is decreased compared to the expression of SMS2 in the cell to which the test substance has not been contacted, selecting the test substance as a treatment substance or prevention substance of the disease associated with amyloid β. 
 
     
     
         3 . A method for screening a treatment substance or prevention substance for a disease associated with amyloid β, comprising:
 (1) allowing a cell to contact with a test substance; 
 (2) comparing an exosome secretion level in the cell to which the test substance has been contacted, with an exosome secretion level in a control cell to which the test substance has not been contacted; and 
 (3) when an exosome secretion level in the cell to which the test substance has been contacted is increased compared to an exosome secretion level in the control cell to which the test substance has not been contacted, selecting the test substance as a treatment substance or prevention substance of the disease associated with amyloid β. 
 
     
     
         4 . The method according to  claim 2  or  3 , wherein said cell and said control cell are a nerve cell. 
     
     
         5 . A pharmaceutical composition for treating or preventing a disease associated with amyloid β, comprising a substance for increasing enzyme activity or expression of protein of N-SMase2. 
     
     
         6 . A pharmaceutical composition for treating or preventing a disease associated with amyloid β, comprising N-SMase2. 
     
     
         7 . A pharmaceutical composition for treating or preventing a disease associated with amyloid β, comprising a substance for suppressing enzyme activity or expression of protein of SMS2. 
     
     
         8 . The pharmaceutical composition according to  claim 7 , wherein said substance is a nucleic acid. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , wherein said nucleic acid is an siRNA and/or antisense nucleic acid. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein said siRNA consists of any one or more selected from the group consisting of siRNAs in the following (a) to (p):
 (a) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 1 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 2;   (b) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 3 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 4;   (c) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 5 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 6;   (d) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 7 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 8;   (e) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 9 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 10;   (f) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 11 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 12;   (g) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 13 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 14;   (h) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 15 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 16;   (i) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 17 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 18;   (j) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 19 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 20;   (k) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 21 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 22;   (l) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 23 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 24, which is a complementary sequence thereof;   (m) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 25 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 26, which is a complementary sequence thereof;   (n) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 27 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 28, which is a complementary sequence thereof;   (o) an siRNA wherein one strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 43 and the other strand of the duplex RNA portion is a base sequence set forth by SEQ ID NO: 44;   (p) an siRNA according to any of (a) to (o), wherein one to several nucleotides are added, inserted, deleted or substituted in one or both of the base sequences, and having an activity of suppressing the expression of SMS2.